ROCKVILLE, Md.—Targeted toward thwarting pathogens known to cause serious infections and diseases, Synthetic Biologics Inc., a developer of anti-infective biologic and drug candidates, has announced positive results from its final preclinical toxicology study of SYN-004, and is in the final stages of preparing its SYN-004 IND application and initiating clinical trials in the fourth quarter of 2014.
The U.S. Food and Drug Administration (FDA) required this “bridging study” to move the company’s lead anti-infective, second-generation product candidate designed to prevent the devastating effects of Clostridium difficile toward the clinic.
If Synthetic Biologics gets a “go” from the FDA, the company plans to follow with a Phase 2 efficacy study in the first half of 2015.
Jeffrey Riley, CEO of Synthetic Biologics, stated in a news release, “As the need for a preventative for C. difficile infections continues to increase globally, moving our SYN-004 program toward the clinic is more important than ever.”
“SYN-004 is unique from other C. difficile preventative approaches in development, as it is designed to protect and maintain the microbiome, and prevent the proliferation and devastating effects of C. difficile infections,” Riley added. “Research continues to demonstrate that protection of the microbiome also plays an increasingly important role in the prevention of a variety of GI, metabolic and CNS disorders. In addition, SYN-004 is provided only when necessary—as a patient receives IV antibiotics and is at greatest risk of developing C. difficile. Synthetic Biologics’ point-of-care preventative approach contrasts significantly with approaches that require mass vaccination.”
C. difficile is classified by the U.S. Centers for Disease Control and Prevention (CDC) as an urgent public health threat given its high prevalence and resistance to many drugs used to treat other infections. It affects 1.1 million Americans annually and creates $8.2 billion in overall annual hospital costs.
C. difficile infections are strongly associated with the use of IV antibiotics, which are administered to more than 24 million Americans annually to prevent or treat infections, the company reported. These powerful antibiotics can create a harmful imbalance in the gastrointestinal tract by wiping out helpful, “good” bacteria, allowing C. difficile to grow out-of-control, leading to severe diarrhea, damaging the colon and, in some cases, causing death.
In the preclinical toxicology study, oral SYN-004 was safe and well tolerated in a canine model over a 28-day dosing period, showing no evidence of toxicity to date at high, repeated doses exceeding those anticipated to be used during human clinical development. These data support Synthetic Biologics efforts to move into clinical development.
As it happens, both Synthetic Biologics and the FDA have friends in high places.
The Obama Administration recently vowed to step up its efforts to combat the rising problem of antibiotic resistance. The president signed an executive order Sept. 18 establishing a new interagency task force charged with developing a national strategy to combat antibiotic-resistant bacteria.
Dr. John Holdren, director of the White House Office of Science and Technology Policy and assistant to President Barack Obama, said the problem is a serious challenge to public health and national security.
“We are clearly in a fight against ... bacteria where no permanent treatment is possible,” he said.
The president’s task force will be co-chaired by the secretaries of the Department of Health and Human Services, the Department of Defense and the Department of Agriculture, and must submit its national five-year action plan to prevent and contain outbreaks and develop the next generation of tests, antibiotics and vaccines by Feb. 15, 2015.
Each year, tens of thousands of deaths and two million illnesses are linked to antibiotic-resistant infections, with impact on the economy as high as $20 billion in direct health care costs, according to the CDC.
But there is light at the end of the tunnel.
The Agency for Healthcare Research and Quality (AHRQ), which provides statistical highlights on the use and cost of health services and health insurance in the United States, reported in 2012:
“Hospital stays involving Clostridium difficile infections, which can cause severe diarrhea, colitis and even death, increased 300 percent between 1993 and 2008, but the number of hospital stays leveled off between 2008 and 2009.”
There were 86,000 hospital stays involving C. difficile in 1993, increasing to 349,000 in 2008, but dropping to 337,000 hospital stays in 2009, the AHRQ reported.
C. difficile is the bacterium that causes an intestinal infection. While normally present in the intestine, this bacterium may dominate when antibiotics are taken, causing inflammation and bleeding in the colon. In its most severe form, C. difficile can be treated only by completely removing the colon.